Vitamin D Modulates Expression of the Airway Smooth Muscle Transcriptome in Fatal Asthma

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Vitamin D Modulates Expression of the Airway Smooth Muscle Transcriptome in Fatal Asthma

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Title: Vitamin D Modulates Expression of the Airway Smooth Muscle Transcriptome in Fatal Asthma
Author: Himes, Blanca E.; Koziol-White, Cynthia; Johnson, Martin; Nikolos, Christina; Jester, William; Klanderman, Barbara; Litonjua, Augusto A.; Tantisira, Kelan G.; Truskowski, Kevin; MacDonald, Kevin; Panettieri, Reynold A.; Weiss, Scott T.

Note: Order does not necessarily reflect citation order of authors.

Citation: Himes, B. E., C. Koziol-White, M. Johnson, C. Nikolos, W. Jester, B. Klanderman, A. A. Litonjua, et al. 2015. “Vitamin D Modulates Expression of the Airway Smooth Muscle Transcriptome in Fatal Asthma.” PLoS ONE 10 (7): e0134057. doi:10.1371/journal.pone.0134057. http://dx.doi.org/10.1371/journal.pone.0134057.
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Abstract: Globally, asthma is a chronic inflammatory respiratory disease affecting over 300 million people. Some asthma patients remain poorly controlled by conventional therapies and experience more life-threatening exacerbations. Vitamin D, as an adjunct therapy, may improve disease control in severe asthma patients since vitamin D enhances glucocorticoid responsiveness and mitigates airway smooth muscle (ASM) hyperplasia. We sought to characterize differences in transcriptome responsiveness to vitamin D between fatal asthma- and non-asthma-derived ASM by using RNA-Seq to measure ASM transcript expression in five donors with fatal asthma and ten non-asthma-derived donors at baseline and with vitamin D treatment. Based on a Benjamini-Hochberg corrected p-value <0.05, 838 genes were differentially expressed in fatal asthma vs. non-asthma-derived ASM at baseline, and vitamin D treatment compared to baseline conditions induced differential expression of 711 and 867 genes in fatal asthma- and non-asthma-derived ASM, respectively. Functional gene categories that were highly represented in all groups included extracellular matrix, and responses to steroid hormone stimuli and wounding. Genes differentially expressed by vitamin D also included cytokine and chemokine activity categories. Follow-up qPCR and individual analyte ELISA experiments were conducted for four cytokines (i.e. CCL2, CCL13, CXCL12, IL8) to measure TNFα-induced changes by asthma status and vitamin D treatment. Vitamin D inhibited TNFα-induced IL8 protein secretion levels to a comparable degree in fatal asthma- and non-asthma-derived ASM even though IL8 had significantly higher baseline levels in fatal asthma-derived ASM. Our findings identify vitamin D-specific gene targets and provide transcriptomic data to explore differences in the ASM of fatal asthma- and non-asthma-derived donors.
Published Version: doi:10.1371/journal.pone.0134057
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514847/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:17820667
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